Biology subjects

McKay, C.

Publications and source records attributed to McKay, C..

3 recordsLinked to original sources

bioRxiv2023

Hi-C assembled genomes of estuarine populations reveal virus-microbe associations and a broad interaction range of a cyanophage

Aquatic microbes play key roles in global biogeochemical cycles and their viral-induced mortality influences the flow of carbon and nutrients between the dissolved and particulate pools. However, many microbes remain uncultivated, hindering understanding of their metabolic capabilities and preventing isolation of viruses that infect them. Here we augment metagenomic sequencing with Hi-C, a proximity-linkage method whereby DNA within a cell is physically bound and then sequenced to link contigs within a metagenome that originated from the same cell. In a size-fractioned water sample from beneath the euphotic zone in a hypoxic estuarine fjord in Puget Sound, WA we resolved 49 proximity-linked bins above 50% complete, including 21 Hi-C Assembled Genomes (HAGs) over 90% complete and a nearly complete genome of the eukaryotic green alga Picochlorum. Viral and microbial sequence within the same HAG identified 18 virus-microbe interactions. A myovirus and a siphovirus were associated with 2 different genera within the Saltatorellus clade of Planctomycetes, a phylum for which no virus has been identified. A partial Phycodnaviridae genome linked to Haptophyte sequence is consistent with contemporaneous observations of a dissipating coccolithophore bloom. A cyanophage S-CAM7-like sequence had a broad interaction range. It was associated with a partial Synechococcus genome in the >3.0 {micro}m size fraction and with a Gammaproteobacteria related to Alcanivorax in the 0.2{micro}m-3.0{micro}m fraction. We suggest that viruses produced in surface waters that are shuttled to depth on sinking aggregates may interact with different hosts in deeper waters, providing an important avenue for gene transfer across broad taxonomic ranges. ImportanceAquatic microbes are important in global elemental cycling. Knowing which viruses infect them in the environment remains a challenge. Using Hi-C, a molecular technique to physically link DNA within a cell, we assembled nearly complete genomes of both prokaryotes and eukaryotes from a hypoxic estuary. Hi-C links captured virus-host interactions for known virus-host pairs and for hosts with no previously known viruses. The same virus was linked to two distinct microbes in different size fractions of water, suggesting it has a broad host range. Viral lysis in surface waters generates sinking particles that deliver newly produced viruses to deeper waters where they interact with different potential hosts, providing an opportunity for gene exchange between unrelated microbes.

microbiology↗

bioRxiv2021

Disentangling Age and Schooling Effects on Inhibitory Control Development: An fNIRS Investigation

Children show marked improvements in executive functioning (EF) between 4 and 7 years of age. In many societies, this time period coincides with the start of formal school education, in which children are required to follow rules in a structured environment, drawing heavily on EF processes such as inhibitory control. This study aimed to investigate the longitudinal development of two aspects of inhibitory control, namely response inhibition and response monitoring and their neural correlates. Specifically, we examined how their longitudinal development may differ by schooling experience, and their potential significance in predicting academic outcomes. Longitudinal data was collected in two groups of children at their homes. At T1, all children were roughly 4.5 years of age and neither group had attended formal schooling. One year later at T2, one group (P1, n = 40) had completed one full year of schooling while the other group (KG, n = 40) had stayed in kindergarten. Behavioural and brain activation data (measured with functional near-infrared spectroscopy, fNIRS) in response to a Go/No-Go task and measures of academic achievement were collected. We found that P1 children, compared to KG children, showed a greater change over time in activation related to response monitoring in the bilateral frontal cortex. The change in left frontal activation difference showed a small positive association with mathematical ability, suggesting certain functional relevance of response monitoring for academic performance. Overall, the school environment is important in shaping the development of the neural network underlying monitoring of one owns performance. Research HighlightsO_LIUsing a school cut-off design, we collected longitudinal home assessments of two aspects of inhibitory control, namely response inhibition and response monitoring, and their neural correlates. C_LIO_LIFor response monitoring, P1 children showed a greater difference over time in activation between correct and incorrect responses in the bilateral frontal cortex. C_LIO_LIThe left frontal activation difference in P1 children showed a small association with mathematical ability, suggesting some functional relevance of response monitoring for academic performance. C_LIO_LIThe school environment plays an important role in shaping the development of the neural network underlying monitoring of one owns performance. C_LI

neuroscience↗

bioRxiv2019

Targeting DNA damage response and Replication Stress in Pancreatic Cancer

Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting the DNA damage response (DDR) and replication stress. We show that patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum and PARP inhibitor therapy in vitro and in vivo. We generated a novel signature of replication stress with potential clinical utility in predicting response to ATR and WEE1 inhibitor treatment. Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=145 SRC=\"FIGDIR/small/713545v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (47K):\norg.highwire.dtl.DTLVardef@106f2b8org.highwire.dtl.DTLVardef@1294d22org.highwire.dtl.DTLVardef@86f5d3org.highwire.dtl.DTLVardef@751e13_HPS_FORMAT_FIGEXP M_FIG C_FIG STATEMENT OF SIGNIFICANCEWe define therapeutic strategies that target subgroups of PC using novel signatures of DNA damage response deficiency and replication stress. This potentially offers patients with DNA repair defects therapeutic options outside standard of care platinum chemotherapy and is being tested in clinical trials on the Precision-Panc platform.

cancer biology↗